Patricia K. Coyle, MD: The Latest on MOG-Mediated Disease in Multiple Sclerosis

In this podcast, Dr Coyle discusses the "final word" on myelin oligodendrocyte glycoprotein-mediated disease in multiple sclerosis from the ECTRIMS/ACTRIMS MSVirtual2020 meeting. A full transcript is provided below.

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Patricia K. Coyle, MD, is a professor in the Department of Neurology at Stony Brook University in New York; director of the Stony Brook MS Comprehensive Care Center; and section editor of multiple sclerosis on Neurology Learning Network.

Transcript:

Christina Vogt: Hello everyone, and welcome back to another podcast. I'm Christina Vogt, managing editor of Neurology Learning Network. Today, I'm joined by Dr Patricia K. Coyle, who is a professor of neurology and director of the Stony Brook MS Comprehensive Care Center at Stony Brook University in New York.

Dr Coyle will be sharing the final word from MSVirtual2020 on myelin oligodendrocyte glycoprotein, or MOG-mediated disease in the context of multiple sclerosis.

Patricia K. Coyle, MD: Let's now discuss MOGAD, the final word from the MSVirtual2020 Meeting. MOGAD or, MOG, myelin oligodendrocyte glycoprotein‑associated disease, is now recognized as a distinct neuroimmune entity, a myelinopathy, and oligodendrogliopathy.

MOGAD is distinct from NMO spectrum disorder. Aquaporin‑4‑positive is the classic feature of NMO spectrum disorder. It's quite distinct from MS, and it's being recognized as its own entity. This came about only in the last few years when it was realized that the accurate assay to detect IgG against MOG required a cell‑based assay and the entire protein.

The first very important abstract that was presented was a retrospective French multicenter study. This has just been published online in the Annals of Neurology. It collected 98 pediatric MOGAD patients and 268 adult MOGAD patients. They were collected from January 2013 to September 2019.

What they concluded, bottom line, is you had to think about pediatric and adult MOGAD differently. They weren't quite identical. In the pediatric cases, the most common symptom was an optic neuritis in 40.8%, followed by acute disseminated encephalomyelitis or ADEM—post‑infectious encephalomyelitis—the second most common syndrome in the pediatric cases at 36.7%.

That was followed by acute transverse myelitis which accounted for 12.2%, brainstem attacks which accounted for 6.1%, and simultaneous optic neuritis and acute transverse myelitis—what we might have thought years ago as a Devic's—in 4.1%.

Now, the pediatric MOGAD cases showed better recovery from their relapses than the adult MOGAD patients. That's not really surprising at all.

When we look at the frequency of MOGAD syndromes in the adult group, overwhelmingly, the most common was optic neuritis at 55.9%. That's the most common in pediatric and in adult and even more enriched in adults. However, the next most common was not ADEM in the adults but the acute transverse myelitis in 25.8%.

That was followed by a dual optic neuritis and acute transverse myelitis in 7.1%, a brainstem syndrome in 5.6% of adults with MOGAD, and then 5.6% of adults had ADEM. That was an unusual presentation.

The adult MOGAD patients have greater risk of relapses than the pediatric MOGAD patients. Now, ultimately in their cohort, 43% lost the antibodies. They lost IgG to MOGAD. They became seronegative. Those that persisted with MOG antibodies were more likely to have relapses, but this was more marked for the pediatric MOGAD cases than the adult MOGAD cases.

They also commented on the spinal fluid profile and said that oligoclonal bands were unusual to find in MOGAD unlike in MS. In fact, the oligoclonal band positivity rate was only in the 11% and 13% range in the pediatric and adult MOGAD cohorts.

Seeing increased white blood cells, a pleocytosis, was common. It was seen in a little over a half, 52 to 54%. Seeing increased total protein was seen in 44% of adults and 24% of the pediatric cases, so really, a different profile than MS spinal fluid.

It's probably worth noting here that MOG‑IgG, we check in blood. That's where it's really enriched. Very unusually, if you truly suspect MOGAD and the blood is persistently negative, you should probably check the antibody in spinal fluid. You may get a yield there.

We also had a very nice discussion about MOGAD from Martin Weber, who pointed out that this was a novel entity that we're still learning about, so the literature is just accumulating.

That bilateral optic neuritis, which is virtually, rarely ever seen in MS—1 to 2%— and is not common at all in aquaporin‑4 NMO spectrum disorder—that was reported in 5 to 41% of MOGAD cases, as high as 41%.

He did emphasize the spinal fluid can be normal in MOGAD cases, so that's possible. Their course is either monophasic, the single attack and nothing else, or relapsing. We do not see a progressive attack. We don't see a progressive, gradually worsening course. He noted that up to 70% of MOGAD patients in their follow‑up would ultimately have a relapse.

He also commented on how steroid‑responsive the MOGAD attacks work, and 50% of people typically will have a complete recovery just with steroids, but then they relapsed after the steroids are stopped.

Another very good discussion from Jackie Palace looked at the prevalence and incidence of MOGAD and NMO spectrum disorder. MOGAD is more common than NMO spectrum disorder. The prevalence that she reported was 20 vs 12 for NMO spectrum disorder per million population. The incidence was 3.4 for MOGAD vs 2 per million population with the NMO spectrum disorder.

In their cohort, 41 to 43% of their MOGAD patients relapsed within a 2‑year timeframe to give you a sense of the risk, and they found that optic neuritis attacks were more likely to relapse.

She reminded us of some of their radiological features—perineuritis inflammation of the optic nerve; the spinal cord conus lesions; in the brain, perhaps more fluffy ADEM‑like lesions as well; and again, no progressive disease.

However, she noted particularly in men that had a transverse myelitis with MOGAD, they could have significant bladder, bowel, and erectile dysfunction issues that could be permanent, even though typically, we think about good recovery from MOGAD attacks.

With regard to treatment, we have of course no FDA‑approved treatment. We don't know the best treatment. The interesting thing is it appears that rituximab, a chimeric anti‑CD20—although you get a response, it's not as good as in NMO spectrum disorder. It's not a wonder drug at all.

She did point out IVIG being very good for pediatric MOGAD. In a recent published analysis, IVIG seemed to have the best response compared to rituximab or other agents.

Christina Vogt: Thanks again for joining me today, Dr Coyle. For more podcasts like this, visit neurologylearningnetwork.com.   

References:

  1. Cobo Calvo A, Ruiz A, Rollot F, et al. Clinical features and risk of relapse in children and adults with myelin oligodendrocyte glycoprotein antibody–associated aisease. Ann Neurol. Published online September 21, 2020. doi:10.1002/ana.25909
  2. Weber M. MOG-mediated disease: Presentation 01. Talk presented at: ECTRIMS/ACTRIMS MSVirtual2020; September 11-13, 2020; Virtual.
  3. Palace J. MOG-mediated disease: Presentation 02. Talk presented at: ECTRIMS/ACTRIMS MSVirtual2020; September 11-13, 2020; Virtual.